Document Detail


Circulating microRNAs as novel biomarkers for platelet activation.
MedLine Citation:
PMID:  23283721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: MicroRNA (miRNA) biomarkers are attracting considerable interest. Effects of medication, however, have not been investigated thus far.
OBJECTIVE: To analyze changes in plasma miRNAs in response to antiplatelet therapy.
METHODS AND RESULTS: Profiling for 377 miRNAs was performed in platelets, platelet microparticles, platelet-rich plasma, platelet-poor plasma, and serum. Platelet-rich plasma showed markedly higher levels of miRNAs than serum and platelet-poor plasma. Few abundant platelet miRNAs, such as miR-24, miR-197, miR-191, and miR-223, were also increased in serum compared with platelet-poor plasma. In contrast, antiplatelet therapy significantly reduced miRNA levels. Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in a dose-escalation study in healthy volunteers at 4 different time points: at baseline without therapy, at 1 week with 10 mg prasugrel, at 2 weeks with 10 mg prasugrel plus 75 mg aspirin, and at 3 weeks with 10 mg prasugrel plus 300 mg aspirin. Findings in healthy volunteers were confirmed by individual TaqMan quantitative real-time polymerase chain reaction assays (n=9). Validation was performed in an independent cohort of patients with symptomatic atherosclerosis (n=33), who received low-dose aspirin at baseline. Plasma levels of platelet miRNAs, such as miR-223, miR-191, and others, that is, miR-126 and miR-150, decreased on further platelet inhibition.
CONCLUSIONS: Our study demonstrated a substantial platelet contribution to the circulating miRNA pool and identified miRNAs responsive to antiplatelet therapy. It also highlights that antiplatelet therapy and preparation of blood samples could be confounding factors in case-control studies relating plasma miRNAs to cardiovascular disease.
Authors:
Peter Willeit; Anna Zampetaki; Katarzyna Dudek; Dorothee Kaudewitz; Alice King; Nicholas S Kirkby; Roxanne Crosby-Nwaobi; Marianna Prokopi; Ignat Drozdov; Sarah R Langley; Sobha Sivaprasad; Hugh S Markus; Jane A Mitchell; Timothy D Warner; Stefan Kiechl; Manuel Mayr
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  Circulation research     Volume:  112     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-15     Completed Date:  2013-04-16     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  595-600     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aspirin / administration & dosage,  pharmacology,  therapeutic use
Biological Markers
Blood Platelets / drug effects,  metabolism*
Blood Specimen Collection / methods
Carotid Artery Diseases / drug therapy
Case-Control Studies
Clinical Trials as Topic
Confounding Factors (Epidemiology)
Diabetes Mellitus, Type 2 / blood
Dose-Response Relationship, Drug
Drug Monitoring
Drug Synergism
Drug Therapy, Combination
Gene Expression Profiling
Humans
Male
MicroRNAs / biosynthesis,  blood*,  genetics
Piperazines / administration & dosage,  pharmacology
Plasma / metabolism*
Platelet Activation* / genetics
Platelet Aggregation Inhibitors / administration & dosage,  pharmacology,  therapeutic use
Platelet-Rich Plasma / metabolism*
Real-Time Polymerase Chain Reaction
Serum / metabolism*
Thiophenes / administration & dosage,  pharmacology
Young Adult
Grant Support
ID/Acronym/Agency:
085255/Z/08/Z//Wellcome Trust; FS/10/37/28413//British Heart Foundation; SP/12/5/29574//British Heart Foundation
Chemical
Reg. No./Substance:
0/Biological Markers; 0/MicroRNAs; 0/Piperazines; 0/Platelet Aggregation Inhibitors; 0/Thiophenes; 34K66TBT99/prasugrel; R16CO5Y76E/Aspirin
Comments/Corrections
Comment In:
Circ Res. 2013 Feb 15;112(4):576-8   [PMID:  23410874 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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